The broad long term goal of this work is to develop sustained release subcutaneous drug delivery systems in order to achieve a more continuous dopaminergic stimulation in the treatment of Parkinson's Disease (PD). The immediate goal of this project is to develop an injectable sustained release formulation for the recently approved anti-Parkinsonian agent apomorphine. Apomorphine is useful in some patients but often requires frequent injections because of its very short half life. We have developed a proprietary subcutaneous sustained release platform technology based on suspensions of polymer-coated pure drug particles. High drug loading and sustained release kinetics have been achieved with several other drugs and this technology has been adapted to apomorphine. The specific aims of the Phase I proposal were: to formulate sustained release suspensions for the dopaminergic agonist apomorphine; to test the in vitro release characteristics of these formulations into buffer; and to test the in vivo pharmacokinetics and the duration of the formulations in rats. The successful completion of these goals is described in the Phase 1 report. We successfully delivered apomorphine in a sustained fashion for 24 hours in rats. The specific aims of this Phase 2 project are to optimize the parameters of the formulation, and to complete the necessary preclinical work to apply for an FDA Investigational New Drug Exemption. The team of investigators is expert in drug development, polymer chemistry, neuropharmacology, pharmacokinetics and clinical neurology. We have experience in collaboration with large pharmaceutical companies leading to the approval of novel drug delivery systems. This project could lead rapidly to the development of an improved injectable dosage form of apomorphine. Completion of these aims will constitute a readily identifiable milestone that will continue in Phase 3, in which we will clarify the potency, duration of action, and safety of the formulation in clinical trials. Apomorphine was approved in 2004 for the treatment of Parkinson's disease. The benefit of this treatment is limited by the very short elimination half life of the drug necessitating frequent injections, which in addition to additional discomfort and inconvenience may actually lead to a progression of the underlying disease. The purpose of this project is to develop a sustained release injectable formulation for this drug that will both increase its effectiveness and reduce its side effects [unreadable] [unreadable] [unreadable]